NDLI: The inducible tissue-specific expression of the human IL-3/GM-CSF locus is controlled by a complex array of developmentally regulated enhancers.

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The inducible tissue-specific expression of the human IL-3/GM-CSF locus is controlled by a complex array of developmentally regulated enhancers.

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The inducible tissue-specific expression of the human IL-3/GM-CSF locus is controlled by a complex array of developmentally regulated enhancers.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hawwari, Abbas Bonifer, Constanze Mirabella, Fabio Bonavita, Aude-Marine Baxter, Euan W. Bert, Andrew G. Cockerill, Peter N. Strogantsev, Ruslan Bertrand, Elisabeth Bowers, Sarion R. West, Adam G. James, Sally R. Gonzalez de Arce, Andrea
Description	Country affiliation: United kingdom Author Affiliation: Baxter EW ( Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Leeds LS9 7TF, United Kingdom.)
Abstract	The closely linked human IL-3 and GM-CSF genes are tightly regulated and are expressed in activated T cells and mast cells. In this study, we used transgenic mice to study the developmental regulation of this locus and to identify DNA elements required for its correct activity in vivo. Because these two genes are separated by a CTCF-dependent insulator, and the GM-CSF gene is regulated primarily by its own upstream enhancer, the main objective in this study was to identify regions of the locus required for correct IL-3 gene expression. We initially found that the previously identified proximal upstream IL-3 enhancers were insufficient to account for the in vivo activity of the IL-3 gene. However, an extended analysis of DNase I-hypersensitive sites (DHSs) spanning the entire upstream IL-3 intergenic region revealed the existence of a complex cluster of both constitutive and inducible DHSs spanning the -34- to -40-kb region. The tissue specificity of these DHSs mirrored the activity of the IL-3 gene, and included a highly inducible cyclosporin A-sensitive enhancer at -37 kb that increased IL-3 promoter activity 40-fold. Significantly, inclusion of this region enabled correct in vivo regulation of IL-3 gene expression in T cells, mast cells, and myeloid progenitor cells.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1201915
Journal	The Journal of Immunology
Issue Number	9
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Enhancer Elements, Genetic Immunology Gene Expression Regulation, Developmental Granulocyte-macrophage Colony-stimulating Factor Biosynthesis Genetics Interleukin-3 Animals Cell Line Cell Line, Tumor Cells, Cultured Deoxyribonuclease I Genetic Loci Jurkat Cells Mice Mice, Transgenic Tissue Distribution Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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